This proposal is submitted for the purpose of further examining the human renal/urinary kinin-forming system and the human vascular fibrinolytic system, their relationships to similar enzymes from other tissues, and their possible roles in renal function and in the development of collagen-vascular disease states. The extensively characterized active site specific anti-urokallikrein available in this laboratory has been used to develop a radioimmunoassay capable of discriminating between latent and active enzyme. This assay, together with a kinin-generating assay, will be used to assess total and active kallikrein in several types of diseases involving impaired renal function. The same antibody, together with specific kinin-generating assays, will be used to isolate latent (trypsin-activatable) kallikrein from human urine which will be characterized relative to the active form of the enzyme. A urinary or renal activator will be sought, purified, characterized and an immunoassay developed and used to examine its contribution to renal function. The availability of monospecific antibody against urinary kallikrein also makes possible the isolation of the antigenically and functionally related enzymes from human pancreas and salivary glands, rigorous re-examination of their physicochemical and functional relationships to renal/urinary kallikrein as well as determination of their specific intra-organ function and localization, activation, and control mechanisms. Further purification and functional characterization of the human vascular plasminogen activator have led not only to a better understanding of its possible presentation in the plasma, but also to modified successful immunization procedures. This activator will be further characterized with regard to activation and control mechanisms and the antibody now available will be used in the development and application of an immunoassay and for tissue localization studies in patients with vasculitis.